The resolution of a mixture of D- and L-phenyl glycine amide by means of an optically active acid is described in co-pending U.S. patent application Ser. No. 623,928 filed Oct. 20, 1975, now U.S. Pat. No. 4,036,852 and U.S. patent application Ser. No. 733,851, filed Oct. 19, 1976. Both of these copending patent applications are by the inventor of the present application, and the entire specification and claims of each is hereby incorporated by reference in the present specification.
The invention relates to an improved process for preparing and isolating a particular optically active phenyl glycine amide by subjecting a mixture of L- and D-phenyl glycine amide to an improved optical resolution treatment. By means of the improved optical resolution treatment, it is possible to isolate improved yields of a desired optically active phenyl glycine amide. As used in the present specification, "a mixture of L- and D-phenyl glycine amide" means either a racemate of phenyl glycine amide, or mixtures of the racemate with either L-phenyl glycine amide or D-phenyl glycine amide.
Phenyl glycine amide can be hydrolized in a simple manner to form phenyl glycine, for example, by treatment with sulfuric acid, as described in the Journal of the Chemical Society, pages 393-97 (1966). Preparation of optically active phenyl glycine has been undertaken by an expensive procedure which includes treating DL-phenyl glycine with .alpha.-bromo-(D-camphor)-sulphonic acid to produce two diastereoisomer salts which are subsequently isolated. This prior procedure is described in Berichte, vol. 41, page 2073 (1908). The prior procedure is laborious and suffers the disadvantage that the .alpha.-bromo-(D-camphor)-sulphonic acid is expensive; the overall cost of the process is further increased because a certain amount of the camphor derivative is lost during the process.
Phenyl glycine amide can be prepared from the amino nitrile of phenyl glycine by hydrolyzing such as amino nitrile with an acid such as hydrochloric acid (see Berichte, vol. 14, page 1968), or by treating phenyl glycine alkyl esters with ammonia (see Journal of the American Chemical Soc., vol. 71 (1949), pages 78, 79). The phenyl glycine alkyl ester may be produced from phenyl glycine nitrile or phenyl glycine.
According to the two copending patent applications incorporated by reference above, it is possible to treat a mixture of L- and D-phenyl glycine amide with an optically active acid to form at least one of the possible diastereoisomer salts, and isolate a desired diastereoisomer salt. The present invention is an improvement inter alia in that the undesired antipode can be easily racemized in accordance with the process described in my copending U.S. patent application Ser. No. 748,398 filed concurrently herewith (incorporated by reference herein) and the resulting racemate subjected to resolution.
The optically active phenyl glycines which can be easily obtained from the resolved optically active phenyl glycine amides are valuable compounds.
For example, D-phenyl glycine is employed as a starting material for the preparation of .alpha.-amino benzyl penicillin. L-phenyl glycine provides a starting material for the sweetening agent L-asparagin-L-phenyl glycine alkyl ester.